An Application of Evidence-Based Marginal Analysis: Assessing the

Advancing Health Economics, Services, Policy and Ethics

An Application of Evidence-Based Marginal Analysis: Assessing the Incremental Cost

Effectiveness of Eras of Metastatic Colorectal Cancer Therapy in British Columbia, Canada:

Pre- and Post-Bevacizumab Introduction

Lindsay Hedden

Priorities 2010, Boston, MA

• This bevacizumab study is part of a larger program of research into Evidence Based Marginal Analysis

– Goal: to develop and pilot novel evidence-based methods for priority setting and resource allocation within the context of cancer control and care in British Columbia

• A key objective: evaluate the effectiveness of priority setting decisions using utilization, mortality, and quality of life data

Priority Setting and Resource Allocation at BCCA

STEERING COMMITTEE– Established and refined decision criteria– Identified three areas for potential resource reallocation– Reviewed results of cost-effectiveness analyses– Made recommendations for resource reallocation

PROGRAM PANELS– Provide clinical and data expertise on model building– Validate results

EMBA Study Structure

• Bevacizumab (bev): given as a first- or second-line systemic therapy in combination with other regimens to treat metastatic colorectal cancer (mCRC)

– 2.8 month average improvement in overall survival

– 2.6 months average improvement in progression-free survival

• National Institute for Health and Clinical Excellence (UK) – £62,857-£88,436 per QALY gained

– Use of bev as first-line therapy is NOT recommended

Bevacizumab (Avastin): Background

• To estimate the incremental cost-effectiveness of bevas a systemic therapy treatment for mCRC, accounting for the differences in costs and health outcomes associated with bevand standard of care treatments

• BUT: Cannot directly compare costs and outcomes for patients treated vs. not treated with bevacizumab because of selection bias

Goal

• Compare eras of treatment for mCRC:

– pre-bevacizumab introduction and post-bevacizumab introduction

– secondary pseudo case-control comparison

• Objectives– 1) To assess the cost-effectiveness of the era of bev protocols in

the treatment of mCRC compared with the pre-bev era

– 2)to evaluate the incremental cost-effectiveness of a first- and second-line bevamong the subset of patients receiving “doublet” chemotherapy (5-FU plus irinotecan or oxaliplatin)

Approach and Objectives

Stage IV Diagnosis

1st Line Chemo

No Chemo

3rd Line Chemo

2nd Line Chemo

Alive

Dead

Markov Model Schema

• Complete cohort of patients presenting with mCRC at diagnosis, identified using BCCA’s Information Service (CAIS)

– Pre-era: Diagnosed Jan 1, 2003-Dec 31, 2004; followed to death, censoring, or Oct 31, 2005

– Bev-era: Diagnosed Jan 1, 2006-Dec 31, 2006; followed to death, censoring, or Oct 31, 2008

• 611 cases in pre-era & 332 in the post-era

Sample

• Survival: derived based on Weibull models

• Chemotherapy: derived based on Exponential models

Transition Probabilities

Chemotherapy Death

No Chemotherapy Death

1st-line 2nd-line

2nd-line 3rd-line

Pre- Post Pre Post Pre Post Pre Post

0.059 0.054 0.093 0.075 0.060 0.086 0.068 0.096

Expense Source Average Cost Per Patient

Pre (n=611) Post (n=332)

Diagnosis &

staging

StatsCan POHEM modeling$2115.38 $2115.38

Day surgeryOntario Case Costing Initiative

$ 1,046.01 $ 1,136.00

InpatientOntario Case Costing Initiative

$ 11,115.13 $ 14,718.00

Systemic

Therapy

BCCA provincial pharmacy

database$ 20,672.62 $ 24,464.53

Radiation

therapy

BCCA radiation oncology

database$ 3,843.40 $ 3,843.40

Costs

State Base-Case Value * Range*

Healthy 1.00 NA

No chemotherapy 0.25 0.20-0.31

Clinical CRC Stage 4 – 1st line chemo 0.25 0.20-0.31

Clinical CRC Stage 4 – 2nd line chemo 0.25 0.20-0.31

Clinical CRC Stage 4 – 3rd line chemo 0.25 0.20-0.31

Dead 0.00 0.00

Utility Values

*Source: Ness, R.M., et al., Outcome states of colorectal cancer: identification and description using patient focus groups. The American Journal of Gastroenterology, 1998. 93(9): p. 1491-1497

Survival for individuals who initiated chemotherapy

0 10 20 30 40

0.0

0.2

0.4

0.6

0.8

1.0

Overall survival time for individuals initiating chemotherapy

Time (months)

Pro

porti

on s

urvi

ving

Pre-Bev: Median = 17.2 months

Bev: Median = 20.1 months

Era Cost / patient Median OS Utilities per patient

Pre$ 34,972 15.6 months 0.34

Post$ 38,764 19.5 months 0.40

Cost/QALY $ 62,468 / QALY Cost/LYG $ 15,617/ LYG

Era-Based Base-Case Results

Sensitivity Analysis

QALY difference

Cos

t diff

eren

ce (t

hous

and

$)

0.000 0.025 0.050 0.075 0.100

-3-1

13

57

• Subset of era-based analysis:

– 1) Diagnosed before age 70

– 2) Treated with first-line doublet chemotherapy

• Intent: include only patients who wereorwould have been eligible for a bev-based protocol

Restricted Analysis

Era Cost per

patient

Median OS Utilities per patient

Pre$ 43,305 18.7 months 0.37

Post$ 45,199 23.1 months 0.41

Cost/QALY $ 43,058 / QALY Cost/LYG $ 10,764 / LYG

Restricted Cohort Base-Case Results

• Era-based: $62,468.68/QALY or $15,617/LYG 3.9 month/patient improvement in survival & $3,791/patient increase in cost

– Not directly inferred as cost-effectiveness of bev

• Other factors my have led to improvements in survival, increases in cost

Interpretation

• Restricted Analysis: $43,058/QALY or $10,764/LYG 4.4 month/patient improvement in survival & $1,894/patient increase in cost

– Closer to a true incremental cost-effectiveness comparing bev with standard of care, but not perfect

• Both methods produced ICERs demonstrating better cost-effectiveness than estimated by NICE

Interpretation (2)

• As a 1st or 2nd line treatment for mCRC, bevmay be relatively cost-effective, considered as part of a suite of available treatments

– the era-based ICER of $62,468 is well in-line with cost-effectiveness ratios reported for other therapies for metastatic cancer therapies

Implications

Acknowledgements

• Project team:

– Dr. Stuart Peacock

– Dr. Diego Villa

– Dr. Hagen Kennecke

• Funding sources:

– CIHR Partnerships in Health Systems Improvement